The long-range objectives of this project are to gain insight into the means of control of bone resorption and to establish more clearly the origin, cell biology, and fate of the osteoclast in normal and osteopetrotic mouse stocks (microphthalmic and grey-lethal). Isolation from the normal mouse spleen of cells possessing the capacity to restore bone resorption in osteopetrotic littermates represents the most important immediate objective of this investigation. This objective arises logically from previous work in which the spleen of normal mice was used as a source of cells which when infused intravenously into cogenitally osteopetrotic littermates restores bone resorption. Research goals for the coming year include: a) To determine which normal mouse spleen cell fractions obtained by unit gravity sedimentation separation have bone-resorption-restoration activity when tested in irradiated osteopetrotic littermates. b) To further assess various properties of osetopetrotic mouse bone including: Origin and acid phosphatase distribution and differentiation of ruffled border of osteoclasts, the origin of marrow cells in parabiotically united osteopetrotic mice and the influence of bone morphogenetic property in the osteopetrotic organism. BIBLIOGRAPHIC REFERENCES: Walker, D.G. Bone resorption restored in osteopetrotic mice by transplants of normal bone marrow and spleen cells. Science 190: 784-785, 1975. Walker, D.G. Spleen cells transmit osteopetrosis. Science 190: 785-787, 1975.